Studies of renin-like activity (RLA) in vessel wall have been plagued by low levels of RLA and nonspecific acid proteases (NAP). Protease inhibitors and affinity chromatography were used to address these problems. The new methods permitted complete separation of RLA from NAP. When sodium depleted rats were studied before nephrectomy and at 2 hours and 24 hours post-nephrectomy, the vascular RLA (devoid of proteolytic activity) fell in parallel with the plasma renin activity (PRA). In animals studied 24 hour after bilateral nephrectomy and 15 hours after hemorrhage the vascular RLA was increased over controls which were nephrectomized and not hemorrhaged. In conclusion the method permitted complete separation of RLA from NAP. After nephrectomy alone, the parallel fall in RLA and PRA suggests that RLA may arise from the plasma. However, the marked increase in RLA after hemorrhage indicates that vascular RLA can be independent of PRA.